Gut microbiota in early life and its impact on allergic diseases

Abstract

This thesis addresses the development of the intestinal microbiota in infancy, investigated by different molecular approaches (all based on rRNA gene analysis), and includes studies describing consequences of early life modulation of microbiota, by supplementation of probiotics, on composition and functionality of the microbiota.

A bacterial population, weighing more than 1.5 kilogram inhabits the adult human intestinal tract: the gut microbiota, comprising approximately 1014 bacteria. The gut microbiota is the ecological community consisting of commensal, symbiotic and pathogenic microorganisms that resides in a defined environment. After birth, infants are rapidly colonized by microbes from different environments they are exposed to. The classical early colonizers of the infant gut are facultative anaerobes of the phylum Proteobacteria, such as Escherichia coli and other Enterobacteriaceae. These organisms pave the way for strictly anaerobic bacteria by depleting the initial available oxygen in a matter of days. The neonatal period comprises a critical period for microbiota development, also because this is the period during which the (mucosal) immune system matures. The long-term composition and function of the newborn’s gut microbiota is suggested to be programmed during this period, thereby laying the foundation for future health and influencing the risk of developing disease later in life. The development of the gut microbiota continues during the first years of life and its composition is considered to resemble the adult gastrointestinal tract by the age of three. Mode of delivery, gestational age and feeding mode especially affect the infant’s microbiota composition. Besides, administration of antibiotics in early life and supplementation with prebiotics or probiotics (live microorganisms that, when administered in adequate amounts, confer a health benefit on the host) can have a major effect on the intestinal microbiota composition. Studies strongly suggest that dysbiosis (disturbance of the microbial balance in the gut) contributes to the development of various kinds of disease, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), obesity, allergy, asthma and diabetes.

The development of the gut microbiota in early life is a complex process, regulated by endogenous as well as exogenous factors, which are being unraveled at the moment but also need additional in-depth investigations. Ultimately, everyone develops his or her own unique, individual microbiota. The vast majority of those microbiota are associated with maintenance of health. In all those cases it is important not to disturb this developmental process in early life (e.g. with antibiotics). When the microbiota develops in an aberrant way, associated with disease, early intervention (e.g. with pre- or probiotics) seems to be warranted. These interventions must be optimized by personalization and targeted application, an approach which now is within reach: the microbiome has the greatest potential to be translated into the clinic in the very short term. The challenge will be to bring this approach into clinical practice.